2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Varying Lymphadenectomies for Gastric
Adenocarcinoma in the East Compared
with the West: Effect on Outcomes
By Benjamin Schmidt, MD, and Sam S. Yoon, MD
Overview: There are notable differences in surgical approaches
to gastric adenocarcinoma throughout the world,
particularly in terms of the extent of lymphadenectomy (LAD).
In high-incidence countries such as Japan and South Korea,
more extensive (e.g., D2) lymphadenectomies are standard,
and these surgeries are generally done by experienced surgeons
with low morbidity and mortality. In countries such as
the United States, where the incidence of gastric adenocarcinoma
is 10-fold lower, the majority of patients are treated at
nonreferral centers with less extensive (e.g., D1 or D0) lymphadenectomy.
There is little disagreement among gastric cancer
(GC) experts that the minimum lymphadenectomy that
should be performed for gastric adenocarcinoma should be at
least a D1 lymphadenectomy, and many of these experts
recommend a D2 lymphadenectomy. More extensive lymphadenectomies
provide better staging of patient disease and
IT IS estimated that there are more than one million cases
of GC worldwide per year, making it the fourth most
common cancer. 1 Nearly three-quarters of cases occur in
developing countries, and nearly half of cases occur in
eastern Asia (mainly in China). GC is the second leading
worldwide cause of cancer death for both men and women,
with a total of more than 700,000 deaths each year. The
incidence of gastric adenocarcinoma varies tremendously
throughout the world and country by country, with the
highest incidence occurring in South Korea at 66.5 to 72.5
per 100,000 males and 19.5 to 30.4 per 100,000 females. 2
The incidence of GC in the United States is only one-tenth
that of South Korea. The estimated number of new GC cases
in the United States in 2012 was 21,320, and the estimated
number of deaths was 10,540. 3
In addition to the global differences in GC epidemiology,
there are also appreciable differences in the surgical treatment
of GC, particularly in the extent of LAD. This article
will examine the effect of varying LADs in Eastern and
Western countries on patient outcomes. Institutional studies
from two countries, Japan and South Korea, will be used
to represent two high-incidence Eastern countries, and institutional
and national database studies from the United
States will be used to represent low-volume Western countries.
Definitions
Before discussion of differences in LAD for gastric adenocarcinoma,
one should define the terms to be used. The node
stations surrounding the stomach were precisely defined by
the Japanese Gastric Cancer Association (JGCA), formerly
known as the Japanese Research Society for Gastric Cancer,
in 1973 4 (Fig. 1 and Table 1). In its most recent GC
treatment guidelines, the JGCA again changed the definitions
for D levels of LAD such that they are now defined
according to the type of gastrectomy performed rather than
the location of the tumor (Table 2). 5 To broadly summarize,
a D1 LAD removes the first tier of perigastric nodes and the
left gastric artery nodes whereas a D2 LAD removes the
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likely reduce locoregional recurrence rates. Two large, prospective
randomized trials performed in the United Kingdom
and the Netherlands in the 1990s failed to demonstrate a
survival benefit of D2 over D1 lymphadenectomy, but these
trials have been criticized for inadequate surgical training and
high surgical morbidity and mortality rates (10% to 13%) in the
D2 group. More recent studies have demonstrated that Western
surgeons can be trained to perform D2 lymphadenectomies
on Western patients with low morbidity and mortality.
The 15-year follow-up of the Netherlands trial now demonstrates
an improved disease-specific survival and locoregional
recurrence in the D2 group. Retrospective analyses and
one prospective, randomized trial suggest that there may be a
survival benefit to more extensive lymphadenectomies when
performed safely, but this assertion requires further validation.
second tier of nodes that generally fall along primary and
secondary branches of the celiac axis (i.e., splenic artery,
common hepatic artery, proper hepatic artery). The JGCA
guidelines recommend a D2 LAD for all gastric carcinomas
beyond a clinical T1 tumor (e.g., tumor invades lamina
propria, muscularis mucosa, or submucosa).
Differences in Surgical Volume and Extent of LAD
Japan and South Korea have two of the highest incidences
of gastric adenocarcinoma in the world, but despite the high
incidence of gastric adenocarcinoma in these countries,
patients are often referred to tertiary centers for treatment.
Two-thirds of all GC surgeries in South Korea are performed
at 16 high-volume institutions, which perform at least 200
GC surgeries per year. Thus GC surgeons at high-volume
institutions in South Korea gain tremendous experience in
the surgical management of GC. As noted earlier, the
minimum LAD performed by Japanese and Korean surgeons
for gastric adenocarcinoma (except for T1 tumors) is a D2
LAD. 5 Despite performing extensive LADs, the morbidity
and mortality rates are quite low. For example, Seoul
National University Hospital (SNUH), which performs almost
1,000 GC operations per year, recently reported a
morbidity rate of 18% and a mortality rate of 0.5%. 6
In contrast, the majority of GC surgeries in the United
States are performed at nonreferral centers. A “high volume”
institution in the United States has been defined in
some studies as centers with as low as more than 15 to 20
surgeries per year. 7,8 Birkmeyer and colleagues reviewed a
database of Medicare patients and found that hospitals with
more than 20 gastrectomies per year had one-third less risk
From the Department of Surgery, Massachusetts General Hospital, Boston, MA; Harvard
Medical School, Boston, MA.
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Sam S. Yoon, MD, Division of Surgical Oncology, Department
of Surgery, Massachusetts General Hospital, Yawkey 7B, 55 Fruit St., Boston, MA 02114;
email: syoon@partners.org.
© 2012 by American Society of Clinical Oncology.
1092-9118/10/1-10